Effects of prolonged anesthesia with dexmedetomidine, fentanyl, or remifentanil on the self-renewal of mouse embryonic stem cells

Abstract

ABSTRACT. Previous study has indicated that exposure to anesthesia in early development leads to neuro-apoptosis and is followed by longterm cognitive dysfunction. Given that larger numbers of pregnant women currently receive anesthesia during the first trimester, we wanted to mimic this process in vitro using mouse embryonic stem cells (mESCs) and to explore how different anesthetics affect the self-renewal of mESCs. In the present study, mESCs were exposed to dexmedetomidine, fentanyl, or remifentanil at clinical concentrations for 48 h. The mESCs were then analyzed for cell proliferation and apoptosis. Furthermore, we used flow cytometry to analyze the cell cycle and quantitative real-time polymerase chain reaction to detect the gene expression during the cell cycle as well as the relevant stemness markers. We found that prolonged anesthesia with dexmedetomidine or fentanyl significantly inhibited mESC proliferation, with fewer cell numbers as well as decreased expression of cyclin B and cyclin E mRNA compared to that in the control group; meanwhile, p21 and RB2 gene expression was increased. Additionally, increases or decreases in the proportion of cells in the G1 and S phases, respectively, were observed in the dexmedetomidine-and fentanyl-treated groups. These anesthetics also repressed the gene expression of mESC stemness makers such as Oct4 and Sox2. However, remifentanil seemed to have no significant influence on the self-renewal of mESCs. These results demonstrated that prolonged anesthesia with dexmedetomidine or fentanyl, but not remifentanil, inhibited mESC proliferation by blocking the G1 to S transition, and repressed the maintenance of mESC stemness.

Effect of Dexmedetomidine in children undergoing general anaesthesia with sevoflurane: a meta-analysis and systematic review

“…35 Dex is a highly selective agonist of a-adrenergic receptors, having sedative, analgesic and anxiolytic effects at clinical doses without affecting the patient's breathing, 30 and it has been widely applied for anaesthesia in children. 7,8,36 Dex induces the activation of a2 receptors and stimulates blue-spot receptors, which can then affect the endogenous sleep pathway, mimicking the sedation that occurs in natural sleep. 37,38 Furthermore, a2 receptors in the spinal cord can also have certain analgesic effects, which will improve the recovery quality after general anaesthesia, probably by mainly reducing the occurrence of agitation during recovery.…”

Evaluation of the Effects of Opium on the Expression of SOX2 and OCT4 in Wistar Rat Bladder

“…Zhang et al observe that fentanyl wasn’t significantly effective in a decrease of the expression of OCT4 and SOX2 , though there was an occasional decrease. In comparison, the expression of OCT4 and SOX2 remained unchanged in the remifentanil treatment groups [ 56 ]. Furthermore, Kocak and colleagues agree with the results, and also showed that the expression of BAX , BCl2 , OCT4 , SOX2 , and Nanog genes in MCF7 cancer stem cells can be decreased with fentanyl treatment.…”

“…So, the observations support the idea that regulation of the cell cycle and maintenance of mESCs can be performed by fentanyl, which leads to its contribution to proliferation and differentiation. Clues extracted from this evidence are useful in rationalizing the mechanisms that explain the effects of fentanyl on mESCs [ 56 ].…”